Chlorosuccinimide → 5-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid methyl ester

HRID 450121Notes

Reaction equation

HRID 450121 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]2[C:13]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=1[F:22])=[O:4].C1C(=O)N([Cl:30])C(=O)C1>C(Cl)Cl.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([Cl:30])=[C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]2[C:13]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=1[F:22])=[O:4]

Participants

5

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 672351107-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid methyl ester

Product 1

HCID 672349105-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid methyl esterYield 48.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid methyl ester (576 mg, 1.40 mmol) in DCM (10 mL) was added NCS (206 mg, 1.54 mmol) and the reaction heated at reflux for 3 hours. More NCS (37 mg, 0.28 mmol) was added and the reaction heated at reflux for 2 hours. The reaction mixture was diluted with water and the product extracted with DCM (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-40% ethylacetate in cyclohexane) to yield the title compound as an off-white solid (300 mg, 48%). LCMS (Method B): RT=4.11 min, M+H+=446.

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 3 hours
  3. temperaturethe reaction heated
  4. temperatureat reflux for 2 hours
  5. extractionthe product extracted with DCM (3×10 mL)
  6. washThe combined organic fractions were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e734a8d5ba9349938b4e6d51ec0a719d
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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